Department of Pathology and Immunology, University of Geneva Faculty of Medicine and Geneva University Hospitals, Switzerland.
Swiss Med Wkly. 2012 Aug 17;142:w13659. doi: 10.4414/smw.2012.13659. eCollection 2012.
Upon reaction with electrons, oxygen is transformed into reactive oxygen species (ROS). It has long been known that ROS can destroy bacteria and destroy human cells, but research in recent decades has highlighted new roles for ROS in health and disease. Indeed, while prolonged exposure to high ROS concentrations may lead to non-specific damage to proteins, lipids, and nucleic acids, low to intermediate ROS concentrations exert their effects rather through regulation of cell signalling cascades. Biological specificity is achieved through the amount, duration, and localisation of ROS production. ROS have crucial roles in normal physiological processes, such as through redox regulation of protein phosphorylation, ion channels, and transcription factors. ROS are also required for biosynthetic processes, including thyroid hormone production and crosslinking of extracellular matrix. There are multiple sources of ROS, including NADPH oxidase enzymes; similarly, there are a large number of ROS-degrading systems. ROS-related disease can be either due to a lack of ROS (e.g., chronic granulomatous disease, certain autoimmune disorders) or a surplus of ROS (e.g., cardiovascular and neurodegenerative diseases). For diseases caused by a surplus of ROS, antioxidant supplementation has proven largely ineffective in clinical studies, most probably because their action is too late, too little, and too non-specific. Specific inhibition of ROS-producing enzymes is an approach more promising of clinical efficacy.
当与电子发生反应时，氧气会转化为活性氧（ROS）。长期以来，人们一直知道 ROS 可以破坏细菌和人类细胞，但近几十年来的研究强调了 ROS 在健康和疾病中的新作用。事实上，虽然长时间暴露于高浓度的 ROS 可能导致蛋白质、脂质和核酸的非特异性损伤，但低至中等浓度的 ROS 通过调节细胞信号级联发挥作用。ROS 通过其产生的数量、持续时间和定位来实现生物学特异性。ROS 在正常生理过程中发挥着至关重要的作用，例如通过氧化还原调节蛋白磷酸化、离子通道和转录因子。ROS 还需要用于生物合成过程，包括甲状腺激素的产生和细胞外基质的交联。ROS 的来源有很多，包括 NADPH 氧化酶；同样，也有大量的 ROS 降解系统。ROS 相关疾病可能是由于 ROS 缺乏（例如慢性肉芽肿病、某些自身免疫性疾病）或 ROS 过剩（例如心血管疾病和神经退行性疾病）引起的。对于由于 ROS 过剩引起的疾病，抗氧化剂补充在临床研究中已被证明效果不大，最可能的原因是其作用为时已晚、作用太小且太非特异性。ROS 产生酶的特异性抑制是一种更有希望具有临床疗效的方法。
